4 research outputs found
Coxsackievirus-B4 Infection of Human Primary Pancreatic Ductal Cell Cultures Results in Impairment of Differentiation into Insulin-Producing Cells
A part of the VP4 capsid protein exhibited by coxsackievirus B4 E2 is the target of antibodies contained in plasma from patients with type 1 diabetes
International audienceThe capsid protein VP4 was identified previously as the target of antibodies contained in plasma enhancing the coxscakievirus B4 (CVâB4) E2âinduced production of IFNâα by peripheral blood mononuclear cells (PBMCs). The sequence of VP4 recognized by these antibodies was investigated. This sequence was identified as amino acids 11 to 30 by using synthetic overlapping peptides spanning VP4CVâB4 E2 in competition experiments for antibodies enhancing the CVB4 E2 induced production of IFNâα by PBMCs. This amino acid sequence was the major target of antiâVP4 antibodies according to enzymeâlinked immunosorbent assays (ELISA). There was a positive correlation between the levels of antiâVP4 and antiâVP411â30 peptide antibodies detected by ELISA. The levels and the prevalences of these antibodies were significantly higher in patients with type 1 diabetes than in healthy controls. The proportions and the levels of those antibodies in patients were independent of HLAâDR alleles, age, or presence of ketosis in blood and were not associated with newly or previously diagnosed disease. The VP4CVâB4 E2 amino acid sequence was submitted to the Swissâmodel in project mode to visualize the possible shape of the sequence of VP4 corresponding to amino acids 11â30 which appeared to be constituted principally by an nonâstructured loop. In conclusion, the sequence of VP4 corresponding to amino acids 11â30, or a part of it plays a role in the plasmaâdependent enhancement of CVâB4 E2âinduced production of IFNâα by PBMCs, suggesting that at 37°C the virus exhibits that region of VP4 to antibodies